25^th World Cancer Conference

Pancreatic ductal adenocarcinoma (PDAC) is a high malignant neoplasm that will represent the second cause for cancer death in the next 20 years. Recent molecular studies have better clarified its complex genetic landscape. However, many mechanisms of tumorigenesis of such tumor remain still unclear and of difficult comprehension. The study of peculiar variants of this tumor type may help in the comprehension of the biology of PDAC. To this aim, we have studied with immunohistochemistry, FISH (Fluorescent in situ hybridization) analysis and whole-exome sequencing the rare PDAC variant named undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UCOGC). Firstly, we observed some clinical and prognostic peculiarities in this PDAC variant. Then we report strikingly molecular similarities of UCOGC to those known to drive conventional PDAC, including activating mutations in the oncogene KRAS, and inactivating mutations in the tumor suppressor genes CDKN2A, TP53, and SMAD4. Lastly, we describe a new potential PDAC driver gene which we found in 25% of UCOGC studied with whole-exome sequencing: the SERPINA3 gene.